Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The data herein demonstrate that in addition to the well-characterized myelin marker-positive, glial fibrillary acidic protein (GFAP)-negative, membrane sheet-bearing oligodendrocytes, another type of myelin marker-positive, process-bearing glia exists in normal and pathologic conditions. This second type of myelin marker-positive glia expresses GFAP, and therefore these cells have been referred to as mixed phenotype glia. Although mixed phenotype glia have been documented previously, their identity and function have remained a mystery. The goal of this immunocytochemical study was to further characterize these cells. Using the MBPlacZ transgenic mouse in which beta-galactosidase is under the control of the myelin basic protein (MBP) gene promoter, GFAP-positive/beta-galactosidase-positive and myelin/oligodendrocyte-specific protein (MOSP)-positive/beta-galactosidase-positive cells were detected in subcortical white matter and in perivascular locations within cerebral white and gray matter. In cultures prepared from highly enriched myelin marker-positive immature glia, mixed phenotype glia were detected that were GFAP-positive and either MOSP-, MBP-, O1-, and O4-positive. The expression of multiple myelin markers by mixed phenotype glia may suggest that these cells are of oligodendrocyte origin. Increased numbers of MOSP-positive/GFAP-positive mixed phenotype glia were detected in sections from adult hypomyelinated brain from shiverer, quaking, and PKU mice compared to myelinated control adult mouse brain. Similarly, cultures from control brain exposed to elevated pH for 2-3 weeks showed dramatically increased numbers of mixed phenotype glia (80%) compared to control (<10%). Increased numbers of mixed phenotype glia also were detected in shiverer cultures (40%). Since increases in the number of mixed phenotype glia occur in shiverer, quaking, and PKU mouse brain, these data suggest that mixed phenotype glia contribute to gliosis in pathologic white matter.
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PMID:GFAP-positive and myelin marker-positive glia in normal and pathologic environments. 1079 44

Focal demyelination models provide powerful tools to study demyelination and remyelination in the central nervous system. In this report, we present a novel technique, which selectively targets oligodendrocytes within the spinal cord of transgenic mice to produce focal demyelination. Transgenic mice expressing the E. coli LacZ (beta-galactosidase) gene from the myelin basic protein promotor allowed for oligodendrocyte-specific cleavage of topically applied fluorescein-di-beta-galactopyranoside liberating photoactivatable fluorescein. Subsequent fluorescence illumination generated oxygen radicals that oxidized a second exogenous substrate, 3-amino-9-ethyl carbazole, to form a toxic precipitate within oligodendrocytes. Histochemical staining of the spinal cord dorsal columns 8 days following phototargeting revealed that the treated region no longer contained beta-galactosidase-positive cells. Focal demyelination of the dorsal columns was observed to a depth of 150 microm in transverse semithin plastic sections. Numerous bundles of naked axons interspersed with myelin, debris-laden macrophages, and reactive astrocytes were evident by electron microscopy. Remyelination of axons by both oligodendrocytes and invading Schwann cells was observed within the treated region 14 days after phototargeting. Newly generated oligodendrocytes were identified within the demyelinated region by their incorporation of bromodeoxyuridine. Thus, this novel focal demyelination protocol provides: (1) a method for selective targeted ablation of oligodendrocytes in vivo, (2) control over the extent of the demyelinated region, with (3) an environment that maintains its remyelination capacity. Phototargeted ablation of oligodendrocytes may therefore be a useful model for studying axon-glia interactions, axon regeneration within a demyelinated zone, and remyelination of axons.
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PMID:Model for focal demyelination of the spinal dorsal columns of transgenic MBP-LacZ mice by phototargeted ablation of oligodendrocytes. 1100 85

We analyzed the role of Fyn tyrosine kinase in CNS myelination by using fyn(-/-) null mutant mice, which express no Fyn protein. We found a severe myelin deficit in forebrain at all ages from 14 d to 1 year. The deficit was maximal at 1 month of age and was similar regardless of mouse strain background or whether it was determined by bulk isolation of myelin or by quantitation of myelin basic protein. To determine the cellular basis of the myelin deficit, we counted oligodendrocytes in tissue sections of mice expressing oligodendrocyte-targeted beta-galactosidase, and we used light and electron microscopy to examine the number and morphology of myelinated fibers and size of myelinated CNS structures. All of these parameters were reduced in fyn(-/-) mice. Unexpectedly, there were regional differences in the myelin deficit; in contrast to forebrain, fyn(-/-) cervical spinal cord exhibited no reduction in myelin content, number of oligodendrocytes, or number of myelinated fibers, nor was myelination delayed developmentally. We found that oligodendrocytes express Src, but there was no significant reduction of myelin content in null mutants lacking the Fyn-related kinases Src, Yes, or Lyn. Finally, we investigated the molecular features of Fyn that are required for myelination and found that a single amino acid substitution, which abolishes the tyrosine kinase activity of Fyn, resulted in a myelin deficit as great as that observed in the complete absence of Fyn protein. These results demonstrate that Fyn plays a unique role in myelination, one that requires its kinase activity.
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PMID:A unique role for Fyn in CNS myelination. 1124 87

Glial cells from neonatal MbetaP5 transgenic mice, which express bacterial beta-galactosidase (lacZ) under control of the myelin basic protein (MBP) promoter (Gow et al, 1992), were transplanted into the spinal cord or cerebral hemisphere of immunosuppressed normal and myelin-deficient (md) rats in order to assess the ability of the donor cells to survive, migrate, and differentiate within normal compared with myelin-deficient central nervous system (CNS). LacZ+ cells were detected as early as 6-7 days after transplantation into the low thoracic cord and by 10 days had spread rostrally to the brainstem and caudally to the sacral spinal cord. Initially, compact lacZ+ cells, lacking processes, were found associated with small blood vessels and with the glia limitans. Cells of this type persisted throughout the experiment. Later, lacZ+ cells with processes were seen along fiber tracts in the dorsal columns and, after intracerebral injection, subjacent to ventricular ependyma, as well as scattered in cerebral white and gray parenchyma. The extent of spread was comparable in md and normal rats, but in the md group, the success rate was higher, and more cells differentiated into process-bearing oligodendrocytes. Acceptance of xenografts in immunosuppressed recipients equaled that of allografts. The overall spread of grafted cells exceeded that of injected charcoal, indicating active migration. In contrast to earlier studies that identified oligodendrocytes based on morphology alone, this study has allowed us to identify and track oligodendrocytes based on myelin gene expression. We show some oligodendrocytes whose morphology is consistent with classical morphological descriptions, some that resemble astrocytes, and a class of compact perivascular oligodendrocyte-lineage cells that we suggest are migratory.
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PMID:Distribution and morphology of transgenic mouse oligodendroglial-lineage cells following transplantation into normal and myelin-deficient rat CNS. 1192 Jul 19

The chronic graft-versus-host (cGvH) reaction is a model of induced lupus caused by alloreactive CD4(+) T cells from a Bm-12 mouse in a C57BL/6 recipient. We used this cGvH reaction in C57BL/6 anti-DNA H chain transgenic mice, 56R/B6, to understand the structure, specificity, and origin of the induced autoantibodies (auto-Abs). We found anti-DNA Abs that reacted to several different antigens, such as phosphatidylserine, myelin basic protein, thyroglobulin, histone, insulin, cytochrome C, and beta-galactosidase. This polyreactivity was found for Abs from B cells that expressed the 56R H chain transgene with "editor" L chains that did not completely veto autoreactivity. We suggest that such incomplete editing results in polyreactivity and that incompletely edited polyreactive B cells influence the subsequent expression of pathogenic auto-Abs in disease. We also found B cells that coexpress kappa and lambda L chain. These B cells contributed to the autoimmune response and are possibly in the marginal zone of the spleen.
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PMID:Light chain editing generates polyreactive antibodies in chronic graft-versus-host reaction. 1680 98

The present study investigated cerebrospinal fluid (CSF) biomarkers for estimating degeneration of the central nervous system (CNS) in experimental dogs with GM1 gangliosidosis and preliminarily evaluated the efficacy of long-term glucocorticoid therapy for GM1 gangliosidosis using the biomarkers identified here. GM1 gangliosidosis, a lysosomal storage disease that affects the brain and multiple systemic organs, is due to an autosomal recessively inherited deficiency of acid beta-galactosidase activity. Pathogenesis of GM1 gangliosidosis may include neuronal apoptosis and abnormal axoplasmic transport and inflammatory response, which are perhaps consequent to massive neuronal storage of GM1 ganglioside. In the present study, we assessed some possible CSF biomarkers, such as GM1 ganglioside, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), neuron-specific enolase (NSE) and myelin basic protein (MBP). Periodic studies demonstrated that GM1 ganglioside concentration, activities of AST and LDH, and concentrations of NSE and MBP in CSF were significantly higher in dogs with GM1 gangliosidosis than those in control dogs, and their changes were well related with the months of age and clinical course. In conclusion, GM1 ganglioside, AST, LDH, NSE and MBP could be utilized as CSF biomarkers showing CNS degeneration in dogs with GM1 gangliosidosis to evaluate the efficacy of novel therapies proposed for this disease. In addition, we preliminarily treated an affected dog with long-term oral administration of prednisolone and evaluated the efficacy of this therapeutic trial using CSF biomarkers determined in the present study. However, this treatment did not change either the clinical course or the CSF biomarkers of the affected dog, suggesting that glucocorticoid therapy would not be effective for treating GM1 gangliosidosis.
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PMID:Cerebrospinal fluid biomarkers showing neurodegeneration in dogs with GM1 gangliosidosis: possible use for assessment of a therapeutic regimen. 1719 62

Using structure based genome mining targeting vascular endothelial and platelet derived growth factor immunoglobulin (Ig) like folds, we have identified a sequence corresponding to a single transmembrane protein with two Ig domains, which we cloned from a human brain cDNA library. The cDNA is identical to hepatocyte cell adhesion molecule (hepaCAM), which was originally described as a tumor suppressor gene in liver. Here, we show that the protein is predominantly expressed in the mouse and human nervous system. In liver, the expression is very low in humans, and is not detected in mice. To identify the central nervous system (CNS) regions and cell types expressing the protein, we performed a LacZ reporter gene assay on heterozygous mice in which one copy of the gene encoding the novel protein had been replaced with beta-galactosidase. beta-galactosidase expression was prominent in white matter tracts of the CNS. Furthermore, expression was detected in ependymal cells of the brain ventricular zones and the central canal of the spinal cord. Double labeling experiments showed expression mainly in CNPase positive oligodendrocytes (OL). Since the protein is predominantly expressed in the CNS glial cells, we named the molecule glial cell adhesion molecule (GlialCAM). A potential role for GlialCAM in myelination was supported by its up-regulation during postnatal mouse brain development, where it was concomitantly expressed with myelin basic protein (MBP). In addition, in vitro, GlialCAM was observed in various developmental stages of OL and in astrocytes in processes and at cell contact sites. In A2B5 positive OL, GlialCAM colocalizes with GAP43 in OL growth cone like structures. Overall, the data presented here indicate a potential function for GlialCAM in glial cell biology.
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PMID:GlialCAM, an immunoglobulin-like cell adhesion molecule is expressed in glial cells of the central nervous system. 1829 12


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